TGF-beta plays an important role in autoimmune diseases, food intolerances, cancer, cognitive function, wound healing and other diseases.
Intro to TGF-Beta
TGF-b is a cytokine that affects the growth and proliferation of many cell types, and it has pro- and anti-inflammatory effects.
TGF-beta is produced in cells such as platelets, macrophages, B- and T-lymphocytes, fibroblasts, ECs, osteoblasts and osteoclasts, astrocytes, and microglial cells. The thymus, bone marrow and bone also produce TGF.
There are different types of TGF, but TGF-b1 is the main one involved in immunity.
TGF-beta is often very elevated in people with biotoxin/mold issues.
Blood TGF is highly significantly correlated with the platelet count, probably because most of the TGF is released by platelets. (R)
You want TGF to be balanced rather than too high or too low…
Summary of Activities of TGF-beta:
- Causes collateral damage in infections
- Causes the growth/changes in tissue
- Decreases acetylcholine
- Decreases slow wave or deep sleep
- Decreases muscle regeneration
- Decreases the action of the vitamin D receptor
- Increases free radicals
- Can decrease bone density
- It inhibits the proliferation of most other cell types
- Suppresses red blood cell formation and lymphocytes (T and B cells)
- Suppresses antibody production
- Suppresses Cytotoxic T Cell (CD8) and Natural Killer cell activity…this can cause viral infections to get out of control.
- Deactivates macrophages
- Promotes oral tolerance
- Suppresses inflammation
- Promotes wound healing and new blood vessel formation (angiogenesis)
- Induces local inflammation and fibrosis
- Stimulates extracellular matrix deposition
- Promotes switch to IgA (R)
- Can increase cancer growth
- Cause negative changes in the airways
- Can benefit cognitive function (when very mildly elevated)
- Can activate EBV or Epstein Barr Virus (R)
The Good (Sometimes)
Studies have shown that TGF-b in the gut area is necessary to create tolerance orally. (R)
The primary mechanisms of oral tolerance are the active suppression of immune responses through the induction of regulatory T cells in the gut-associated lymphoid tissue. These Th3 cells secrete TGF-b, IL-4, and IL-10, which decrease Th1 and other immune cells.
TGF-b also leads to the death of T cells that attack our tissue (clonal deletion). (R)
Due to its potent anti-proliferative effects, TGF-b normally functions as a tumor suppressor. However, cancer cells develop resistance to TGF-beta late in tumor progression by using multiple mechanisms.
TGF-b promotes wound healing due to its unique effect on the extracellular matrix by stimulating the synthesis of matrix proteins and decreased matrix degradation.
In infections, it protects against collateral damages caused by the immune system, but it also promotes immune evasion by pathogens and therefore can lead to chronic infections.
TGF-b suppresses the immune system at the systemic level but stimulates the immune and inflammatory responses at the local level.
TGF-b1 deficient mice develop an inflammatory response with massive white blood cell infiltration in numerous organs, accompanied by increased expression of TNF-a, IFN-g, and class I and II MHC antigens, resulting in death at 3 to 5 weeks. These mice also have high levels of autoantibodies. Thus, TGF-b1 normally acts as an active suppressor of inflammation.
TGF-b can suppress the proliferation of T- and B-lymphocytes, monocytes, and macrophages.
It suppresses immunoglobulin (Ig) secretion of mature B cells, but can increase IgA production (not a cause of autoimmunity).
TGF-b can deactivate macrophages by reducing their capacity to release superoxide and nitric oxide, suppressing their cytotoxic activity, decreasing their expression of MHC class II, inhibiting the production of TNF-a and IL-1, and antagonizing the effects of these cytokines.
TGF-beta inhibits mast cells (R).
TGF-b can also benefit cognitive function. One study found TGF-beta was associated with increased cortical thickness, and this is thought in part to do with the reduction of cytokines. (R)
TGF is low in advanced atherosclerosis.
TGF-b can increase inflammation locally.
TGF-b suppresses red blood cells by inhibiting bone marrow stem-cell proliferation and decreasing the expression of receptors for IL-3, and GM-CSF on hematopoietic cells (R).
One thing that is interesting is that I have a client/friend with high TGF and low RBCs. This makes sense because TGF decreases RBC formation.
In cancer, TGF-β is a potent inhibitor of cell proliferation and acts as a tumor suppressor at the beginning of tumor formation. However, once the cells become resistant to TGF-β, it mainly supports tumor growth and metastasis by promoting immune evasion and angiogenesis. (R)
TGF-b decreases muscle regeneration (R), which is one reason why people with CIRS lose muscle.
Indeed, an elevated blood level of TGF-b significantly correlated with lymph node metastasis and poor prognosis in patients with gastric cancer. (R)
TGF-b causes various cells to stick to the site of inflammation and tissue injury (chemotaxis). These include neutrophils, monocytes, lymphocytes, mast cells, and fibroblasts; TGF-beta also activates these cells to produce inflammatory cytokines (IL-1, TNF, and IL-6); and causes white blood cells to stick to the vessel wall and Extracellular matrix.
TGF-b has both positive and negative effects on bone mineral density. It’s thought by scientists that in the short term in can help bone density, but chronically elevated TGF-b will decrease bone density. (R)
TGF-b has been proposed as a contributing factor in many chronic inflammatory diseases, which include rheumatoid arthritis, glomerulonephritis, pulmonary fibrosis, systemic sclerosis, and chronic hepatitis.
TGF-b is elevated in the blood of patients with invasive prostate cancer.
These inhibit TGF in different places, but not necessarily systemically….
- PPAR gamma and PPAR alpha agonists (R, R2, R3, R4) – reduces TGF in blood vessels and the negative effects of TGF in skin, heart muscle, and liver cells… PPAR gamma can be considered anti-TGF overall.
- Vitamin D Receptor activation (R), Angiotensin II type 1 receptor antagonist (R)
- Sun/UV (R, R2) – at least in skin cells
- Klotho – Specifically, Klotho was shown to bind to the TGF-β1 receptor to inhibit TGF-β1 binding (R).
- Curcumin (R)
- Black Cumin Seed Oil /Thymoquinone (R) -in rat model of allergic airway inflammation
- Andrographis/Andrographolide (R)
- Ursolic acid (R)
- Extra Virgin Olive Oil (R)
- Reishi (R)
- Fucoidan (R)
- Resveratrol (R)
- Apigenin (R)
- Berberine (R)
- Grape Seed Extract
- Ginkgo (R)
- Pregnenolone (R)
- Astragalus (R, R2)
- Gotu Kola /Asiatic Acid,
- Emodin (found in Fo-Ti, Resveratrol, Rhubarb, Aloe)
- Theanine (R)
- Ginseng (R)
- Kudzu root/Puerarin
- Angelica S, Hydrangea, Dan Shen, Almond, Cordyceps, Butein, Betulinic acid
- Enterococcus faecalis (R)****
- Growth factors inhibited a TGFbeta1 increase in specific cellular models: IGF-I, EGF and Growth Hormone (cellular model) (R)
- Hypoxia (R) or low oxygen
- Psychological stress in primates (R, R2) and in the rat hippocampus (R). Psychological stress increases TGF-beta through catecholamines (epinephrine, norepinephrine, and dopamine) (R).
- Wounds and burns (R, R2),
- SIRT1 (R) – maybe resveratrol is not a great idea
- Pregnenolone (R),
- Growth Hormone (R)
- 5HT2A Receptors
- Estrogen (R, R) – increased TGF in skin
- T3 (R)
- Cigarette smoke (R)
- Progesterone (R, R2, R3) – increased TGF in epithelial cells…which are all over the body…
- Somatostatin (R)
- Mast cells release TGF-beta (R)
- Interferon (R)
- S Boulardii (R) – TGF increased in the blood in chicks.
- Bacillus Subtilis (R) – TGF increased in the blood in chicks.
- Artemisinin (R) – increased TGF in spleen cells,
- AngiotensinII- increased TGF in heart (R),
- Beta-2 Adrenoreceptor (R) agonist increased TGF in the hippocampus…
- Endoplasmic reticulum stress (R)
How to Increase Intestinal TGF-beta
- Ingesting TGF-beta itself (R)…Colostrum (R) and breast milk have TGF-beta.Cyplexinol is a source of TGF-beta as well.
- IGF-1 (R) –Cyplexinol, Colostrum (R) and Antler velvet have this….Increased TGF in intestines.
- LLLT (R, R2, R3), LLLT seems to increase TGF-beta in various places. Put on your intestines for 5-10 minutes. According to Dr. Hamblin, though, it probably won’t get through…
- Pancreas/Ingesting insulin (R), – increases TGF in intestines…
- Cinnamon (R) – by increasing regulatory Dendritic Cells
- Curcumin (R), – in the intestines
- Retinol (R), – in the intestines
- Berberine (R) maybe…..GLP-2 (R) and DPP4 inhibitors (R)
- Nucleotides (R) – in the intestines
- Bile (R)...also Bile Acid Conjugates/TUDCA and Liver
- Probiotics: Lactobacillus rhamnosus (R),
- Lactoferrin (R) – in mesenteric lymph node cells in intestines
- Honokiol (R) – increased TGF-b in the lungs of animal models with chronic asthma.
- 1,25 Vitamin D3 (Active form) (R) – increased TGF in blood….1,25 Vitamin D3 caused CD8+ T cells to secrete more TGFb (R, R2)
- Shikonin (R) – increased TGF in intestines,
- VEGF (R) – increased TGF in intestines.
TGF-beta and Mold
I’m not completely sure why TGF is elevated in people with mold issues. It could be TGF is an attempt by the body to create oral tolerance, but it doesn’t have other necessary ingredients or the proper anti-inflammatory environment. It then gets out of control and can be quite damaging.
This will contribute to a state of low oxygen or hypoxia.
It also turns out that low oxygen can increase TGF, at least in some cells. (R)
This person does very well with hyperbaric oxygen therapy, which can help in part by decreasing TGF-beta.
The Genetics of TGFbeta1
You can find the TGFbeta1 gene on SelfDecode with 7 SNPs on the 23andme chip. SelfDecode is a program that allows you to analyze and deconstruct your genetics and uncover health information about yourself in order to make you more optimal.
If you upload your file you can see what your genetics are (I pasted my file here, so my SNPs show):
- RS1800469 (TGFB1) AA
- RS1800470 (TGFB1) — Healthy controls carrying rs1800470 TT genotype had 191 pg/ml, while the CC genotype had 129.4 pg/mL (R).
- RS1800471 (TGFB1) CC
- RS1800472 (TGFB1) GG
- RS2241715 (TGFB1) AA
- RS4803455 (TGFB1) CC
- RS8110090 (TGFB1) AG